Emerging epigenomic landscapes of pancreatic cancer in the era of precision medicine

Abstract

Genetic studies have advanced our understanding of pancreatic cancer at a mechanistic and translational level. Genetic concepts and tools are increasingly starting to be applied to clinical practice, in particular for precision medicine efforts. However, epigenomics is rapidly emerging as a promising conceptual and methodological paradigm for advancing the knowledge of this disease. More importantly, recent studies have uncovered potentially actionable pathways, which support the prediction that future trials for pancreatic cancer will involve the vigorous testing of epigenomic therapeutics. Thus, epigenomics promises to generate a significant amount of new knowledge of both biological and medical importance.

Basal-like and Classical cells coexistence in pancreatic cancer revealed by single cell analysis

“…40 41 42With a survival rate of 5 years in less than 8% of the cases (Siegel et al, 2018) pancreatic 43 ductal adenocarcinoma (PDAC) is still one of the most lethal cancers. A principal problem 44 facing this disease is its heterogeneity that results as a consequence of the combination of 45 genetic, epigenetic, and micro-environmental factors (Lomberk et al, 2019(Lomberk et al, , 2018 Yachida and 46 Iacobuzio-Donahue, 2013). Recently, two main PDAC subtypes have been identified by 47 molecular characterization: 1-classical, that are more frequently resectables, presenting a 48 higher level of differentiation, often associated with fibrosis and inflammation; and 2-basal-49 like, with a poorest clinical outcome and a loss of differentiation (Moffitt et al, 2015; Nicolle 50 et al, 2017).…”

Organoïdes dérivés des adénocarcinomes pancréatiques

“…L'utilisation d'approches « gènes candidats » a en effet permis dans un premier temps, d'identifier l'activation d'oncogènes ( [5]. Les approches portant sur l'ensemble du génome ont, par la suite, abouti à l'identification de nouvelles mutations somatiques, de variations du nombre de copies de certains gènes, de variations structurelles et d'altérations épigénétiques [6][7][8][9] (➜). Malgré ces énormes progrès dans la compréhension des mécanismes reliés à la pathogenèse du PDAC, l'impact sur la prise en charge des patients est resté limité.…”

The Emerging Roles of ATP-Dependent Chromatin Remodeling Complexes in Pancreatic Cancer

“…ATP-dependent chromatin remodeling complexes have essential functions during development; therefore, it is not surprising that genomic aberrations in genes encoding chromatin remodeling components contribute to different malignancies, such as cancer, including PDAC [6,32,33,35,[43][44][45]. Epigenetic reprogramming has significant roles in lineage specification during pancreas development, and the development-specific subunit expression is important for altering the functional activity of the complexes [46][47][48][49].…”

“…In addition to the mutations in the main oncogenes and tumor suppressors, the influence of the epigenetic dysregulation has been identified and is now increasingly being studied. Multiple studies highlighted the involvement of epigenetic dysregulation in cancer development, progression, and chemoresistance [3][4][5][6][7][8][9]. Epigenetics are changes that result in changes of gene expression without altering the DNA sequence and involve nucleosome remodeling, histone modifications, DNA methylation, and regulation through long noncoding RNAs (Figure 1).…”